Biology subjects

Xu, S.

Publications and source records attributed to Xu, S..

At least 199 records · Page 11Linked to original sources

bioRxiv2024

Cost-effective DNA storage with DNA movable type

In the face of exponential data growth, DNA-based storage offers a promising solution for preserving big-data. However, most existing DNA storage methods, akin to traditional block printing, require costly chemical synthesis for each individual data file, adopting a sequential, one-time-use synthesis approach. To overcome these limitations, we introduce a novel, cost-effective "DNA-Movable-Type Storage" system, inspired by movable type printing. This system utilizes pre-fabricated DNA movable types-short, double-stranded DNA oligonucleotides encoding specific payload, address, and checksum data. These DNA-MTs are enzymatically ligated/assembled into cohesive sequences, termed "DNA movable type blocks", streamlining the assembly process with the automated BISHENG-1 DNA-MT inkjet printer. Using BISHENG-1, we successfully printed, assembled, stored and accurately retrieved 43.7 KB of data files in diverse formats (text, image, audio, and video) in vitro and in vivo, using only 350 DNA-MTs. Notably, each DNA-MT, synthesized once (2 OD), can be used up to 10,000 times, reducing costs to 122 $/MB-outperforming existing DNA storage methods. This innovation circumvents the need to synthesize entire DNA sequences encoding files from scratch, offering significant cost and efficiency advantages. Furthermore, it has considerable untapped potential to advance a robust DNA storage system, better meeting the extensive data storage demands of the big-data era.

bioinformatics↗

bioRxiv2024

Single-Cell and Spatial Transcriptomic Analyses Deciphering the Three-Layer Architecture of Human Tuberculosis Granulomas

BackgroundGranulomas (defining tuberculosis histopathological feature) are central to the hosts defense against Mycobacterium tuberculosis, critically influencing patient outcomes. However, knowledge of human granulomas structure and function are incomplete. This study employs single-cell and spatial transcriptomics to dissect human granulomas cellular composition, structure, communication and function from 19 pulmonary, lymphatic and skeletal samples. ResultsOur study identified nine key immune-activated/signaling-active cell clusters. Notably, we delineated a three-layered granuloma structure: a core with macrophages (Macro-c09, Macro-c10) and occasional fibroblasts (Fib-c03); a fibroblast-rich (Fib-c01) periphery; and an immune-infiltrated intermediate layer comprising diverse immune-cells recruited by strong signaling-molecules (SPP1/MIF) from core/periphery cells. This study also shows granuloma heterogeneity across individuals and tissues. ConclusionsBy merging scRNA-seq with ST-seq, we offer an intricate single-cell perspective of granulomas spatial-structure and formation mechanisms, identify signaling-molecules and significantly changed genes as potential targets for host-directed tuberculosis immunotherapy, highlight fibroblasts crucial role in granuloma formation, and provide an important reference/improved understanding of TB.

microbiology↗

bioRxiv2024

THE MOLECULAR MECHANISMS OF DEFENSIVE-GRADE ORGANIC ACID BIOSYNTHESIS IN GROUND BEETLES

Insects are known to synthesize and secrete hundreds of unique defensive chemicals, including caustic acids, pungent phenolics, and citrusy terpenes. Despite efforts to characterize the defensive chemistry of ground beetles (Coleoptera: Carabidae), our knowledge of semiochemical evolution within the family and how these compounds are biosynthesized remains limited. Few studies have demonstrated the likely biosynthetic precursors of select compounds in certain taxa, and only one has demonstrated which genes may be involved in the biosynthesis of formic acid. Here, we characterize the defensive chemistry and generate defensive gland transcriptomes for ground beetle species representing two defensive chemical classes: the formic acid producer Platynus angustatus and the methacrylic acid producer Pterostichus moestus. Through comparative transcriptome analyses, we demonstrate that co-option of distinct primary metabolic pathways may be involved in formic acid and methacrylic acid biosynthesis in the defensive glands of these taxa. These results expand our knowledge of ground beetle defensive chemistry and provide additional evidence that co-option of existing primary metabolic pathways plays a major role in the evolution of ground beetle chemical defense.

evolutionary biology↗

bioRxiv2024

BEACON: Benchmark for Comprehensive RNA Tasks and Language Models

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA, particularly universal RNA language models, there remains a significant lack of standardized benchmarks to assess the effectiveness of these methods. In this study, we introduce the first comprehensive RNA benchmark BEACON (BEnchmArk for COmprehensive RNA Task and Language Models). First, BEACON comprises 13 distinct tasks derived from extensive previous work covering structural analysis, functional studies, and engineering applications, enabling a comprehensive assessment of the performance of methods on various RNA understanding tasks. Second, we examine a range of models, including traditional approaches like CNNs, as well as advanced RNA foundation models based on language models, offering valuable insights into the task-specific performances of these models. Third, we investigate the vital RNA language model components from the tokenizer and positional encoding aspects. Notably, our findings emphasize the superiority of single nucleotide tokenization and the effectiveness of Attention with Linear Biases (ALiBi) over traditional positional encoding methods. Based on these insights, a simple yet strong baseline called BEACON-B is proposed, which can achieve outstanding performance with limited data and computational resources. The datasets and source code of our benchmark are available at https://github.com/terry-r123/RNABenchmark.

bioinformatics↗

bioRxiv2024

Hypothalamic prostaglandins facilitate recovery from hypoglycemia but exacerbate recurrent hypoglycemia in mice

The hypothalamus monitors blood glucose levels and regulates glucose production in the liver. In response to hypoglycemia, glucose-inhibited (GI) neurons trigger counter-regulatory responses (CRRs), which stimulate the release of glucagon, epinephrine, and cortisol to elevate blood glucose. Recurrent hypoglycemia (RH), however, reduces the effectiveness of these CRRs. This study examined the role of hypothalamic prostaglandins in glucose recovery during acute hypoglycemia and RH. Using imaging mass spectrometry and liquid chromatography/mass spectrometry, phospholipid and prostaglandin levels in the hypothalamus of C57BL mice were increased following insulin or 2-deoxy-glucose administration. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), was infused into the ventromedial hypothalamus (VMH) to analyze its effect on glucose production during hypoglycemia, revealing that prostaglandin inhibition decreased glucagon secretion. Additionally, RH-treated mice decreased glucagon release and glucose production during hypoglycemia. Inhibiting prostaglandin production via short-hairpin RNA against cytosolic phospholipase A2 (cPLA2) in the hypothalamus restored CRRs diminished by RH via increasing glucagon sensitivity. These findings suggest that hypothalamic prostaglandins play a critical role in glucose recovery from acute hypoglycemia by activating VMH neurons and are also crucial for the attenuation of CRRs during RH. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/600540v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@9e2cf0org.highwire.dtl.DTLVardef@984c29org.highwire.dtl.DTLVardef@b04e6borg.highwire.dtl.DTLVardef@ec6dd3_HPS_FORMAT_FIGEXP M_FIG C_FIG Article HighlightsO_LIInsulin decreases arachidonic acid-containing phospholipids and increases prostaglandin production in the hypothalamus. C_LIO_LIProstaglandin in the hypothalamus increases glucagon secretion and glucose production during hypoglycemia. C_LIO_LIRecurrent hypoglycemia decreases glucagon secretion and glucose production during hypoglycemia. C_LIO_LIProstaglandin in the hypothalamus during recurrent hypoglycemia decreases glucagon sensitivity and glucose production. C_LI

neuroscience↗

bioRxiv2024

Blocking HXA3-mediated neutrophil elastase release during S. pneumoniae lung infection limits pulmonary epithelial barrier disruption and bacteremia

Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin (PLY), triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface (ALI) cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant fMLP did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia. ImportanceStreptococcus pneumoniae (Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses to Sp. Excessive polymorphonuclear leukocyte (PMN) infiltration into Sp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflect bona fide lung epithelium, we identified the eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment for Sp lung infection.

microbiology↗

bioRxiv2024

RTM-align: an improved RNA alignment tool with enhanced short sequence performance via post-standardization and fragment alignment

Understanding the three-dimensional structure of RNA is crucial for studying various biological processes. Accurate alignment and comparison of RNA structures are essential for illustrating RNA functionality and evolution. The existing RNA alignment tools suffer from limitations such as size-dependency of scoring functions and inadequate handling of short RNA fragments, leading to the conflicting interpretation of structural and functional relationships among RNA molecules. Hence, we introduce RTM-align, a novel RNA structural alignment tool enhanced for short RNAs. RTM-align employs the RTM-score, which integrates post-standardization to ensure size-independence and utilizes a fragment alignment strategy that improves alignment accuracy by concentrating on structural motifs and local structural elements. Benchmarking results demonstrate that RTM-align outperforms existing tools in RNA structure comparison, offering a universal scoring scale regardless of RNA length. The improvement is particularly evident in evaluating predicted structures for CASP15 RNA targets, with significant enhancements observed for the short RNA target R1117. RTM-align is expected to significantly improve the accuracy and reliability of RNA structure alignment and comparison, thereby aiding in the deeper understanding and discovery of novel RNA functions and their interactions in biological systems. RTM-align is now available at https://github.com/BEAM-Labs/RTM-align.

bioinformatics↗

bioRxiv2024

Differential prevalence and risk factors for infection with coronaviruses in bats collected during 2020 in Yunnan Province, China

Coronaviruses (CoVs) pose a threat to human health globally, as highlighted by severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the COVID-19 pandemic. Bats from the Greater Mekong Subregion (GMS) are an important natural reservoir for CoVs. Here we report the differential prevalence of CoVs in bats across biological and ecological factors within Yunnan Province. We also show the coexistence of CoVs in individual bats and identify an additional putative host for SARS-related CoV, with higher dispersal capacity than other known hosts. Notably, 11 SARS-related coronaviruses (SARSr-CoVs) were discovered in horseshoe bats and a Chinese water myotis bat by pan-CoV detection and Illumina sequencing. Our findings facilitate an understanding of the fundamental features of the distribution and circulation of CoVs in nature as well as zoonotic spillover risk in the One health framework.

microbiology↗

bioRxiv2024

Pi-PrimeNovo: An Accurate and Efficient Non-Autoregressive Deep Learning Model for De Novo Peptide Sequencing

Peptide sequencing via tandem mass spectrometry (MS/MS) is fundamental in proteomics data analysis, playing a pivotal role in unraveling the complex world of proteins within biological systems. In contrast to conventional database searching methods, deep learning models excel in de novo sequencing peptides absent from existing databases, thereby facilitating the identification and analysis of novel peptide sequences. Current deep learning models for peptide sequencing predominantly use an autoregressive generation approach, where early errors can cascade, largely affecting overall sequence accuracy. And the usage of sequential decoding algorithms such as beam search suffers from the low inference speed. To address this, we introduce{pi} -PrimeNovo, a non-autoregressive Transformer-based deep learning model designed to perform accurate and efficient de novo peptide sequencing. With the proposed novel architecture,{pi} -PrimeNovo achieves significantly higher accuracy and up to 69x faster sequencing compared to the state-of-the-art methods. This remarkable speed makes it highly suitable for computation-extensive peptide sequencing tasks such as metaproteomic research, where{pi} -PrimeNovo efficiently identifies the microbial species-specific peptides. Moreover,{pi} -PrimeNovo has been demonstrated to have a powerful capability in accurately mining phosphopeptides in a non-enriched phosphoproteomic dataset, showing an alternative solution to detect low-abundance post-translational modifications (PTMs). We suggest that this work not only advances the development of peptide sequencing techniques but also introduces a transformative computational model with wide-range implications for biological research.

bioinformatics↗

bioRxiv2024

Structural insights into transcription regulation of the global virulence factor PhoP from Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), remaining as the leading cause of the worldwide threat Tuberculosis, relies heavily on its transcriptional reprogramming of diverse stress genes to swiftly adapt to adverse environments and ensure infections. The global virulence factor PhoP plays a pivotal role in coordinating transcription activation or repression of the essential phosphate-nitrogen metabolic remodeling genes. However, what defines PhoP to deferentially act as an activator or a repressor remains largely unexplored. Here, we determine one cryo-EM structure of Mtb RNAP-promoter open complex, three cryo-EM structures of PhoP-dependent transcription activation complexes (PhoP-TACs) consisting of Mtb RNA polymerase (RNAP), different number of PhoP molecules binding to different types of well-characterized consensus promoters, and one cryo-EM structure of Mtb PhoP-dependent transcription repression complex (PhoP-TRC) comprising of Mtb RNAP, PhoP, the nitrogen metabolism regulator GlnR and their co-regulated promoter. Structural comparisons reveal phosphorylation of PhoP is required for stabilization of PhoP-TACs, PhoP specifically recognizes promoters as novel tandem dimers and recruits RNAP through extensively interacting with its conserved {beta} flap and {sigma}AR4 domains. Strikingly, the distinct promoter spacer length and PhoP-GlnR interactions in PhoP-TRC constrain the upstream DNA into a distinct topology and retain PhoP in a novel dragging repression mode. Collectively, these data highlight the dual regulatory mechanisms of PhoP-dependent transcription regulation in governing stress adaptation. These findings provide structural basis for developing potential anti-tuberculosis drugs and/or interventions.

microbiology↗

bioRxiv2024

Improvement in Outcomes and Prevention of Multiple Organ Dysfunction Syndrome After Cardiac Arrest and Successful Cardiopulmonary Resuscitation by Systemic Administration of Bumetanide in Male Mice

BACKGROUNDCardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) cause post-CA brain injury (PCABI) and extracerebral multiple organ dysfunction (EMOD), leading to low survival and disability in resuscitated patients. The pathogenesis of PCABI is still poorly understood, and no therapeutic-related factors have been identified to improve survival and neurological outcomes to date. Bumetanide is a promising pharmaceutical intervention for some neurological disorders that have some common pathophysiology with PCABI, and it also exhibit systemic protective effects on vital organs under pathological conditions. This study aims to investigate the protective effects of bumetanide on PCABI and EMOD after CA/CPR, and uncover the pathogenesis and biomarkers of PCABI at protein level. METHODSWe generated a hyperkalemia-induced asystole CA/CPR mouse model with bumetanide/vehicle treatment after resuscitation. Survival, neurological outcome, functional outcome, key pathophysiological process underlying PCABI, and injury level of EMOD were evaluated. Proteomics analysis of cerebral cortex was performed for investigating mechanisms of PCABI. RESULTSBumetanide significantly improved outcomes after CA/CPR and reduced the main pathophysiological processes of PCABI, including seizures, neurodegeneration, neuroinflammation, decreased cerebral blood flow, blood-brain barrier disruption, and oxidative stress. CA/CPR-induced injury in heart, lung, liver, kidney, spleen, adrenal gland, spinal cord, pennis, and urinary bladder were also alleviated by bumetanide. Proteomic study and experimental verification identified LCN2/NGAL is a potential biomarker for early neuroprognostication and has association with PCABI severity. CONCLUSIONSSystemic administration of bumetanide improved outcomes and prevented multiple organ dysfunction after CA/CPR. LCN2/NGAL is a novel biomarker for early neuroprognostication at 24 hours after CA/CPR. Clinical PerspectiveO_LIWhat Is New? O_LIPost-resuscitation bumetanide treatment could improve outcomes and prevent brain injury and extracerebral multiple organ dysfunction after hyperkalemia-induced asystole cardiac arrest in mice. C_LIO_LINeuronal subpopulations in cerebral cortex were selectively vulnerable, and all major organs had obvious tissue damage with inflammatory cell infiltration and tissue edema after resuscitation. C_LIO_LIThis the first study to identify the pathogenesis and biomarkers of post-cardiac arrest brain injury with proteomic studies, and LCN2/NGAL had a strong and graded association with pathogenesis of PCABI, which could be a marker for monitoring and neuroprognostication. C_LI C_LIO_LIWhat Are the Clinical Implications? O_LIBumetanide may be a novel pharmacological therapy to improve survival and neurological outcomes in post-resuscitation care, and cerebral-specific quantification of LCN2/NGAL could be used for early neuroprognostication at 24 hours after cardiac arrest. C_LIO_LIExtracerebral multiple organ injury is common and severe after resuscitation, which needs to be given more attention in clinical management. C_LI C_LI

physiology↗

bioRxiv2024

Unraveling the Interplay between Stability and Flexibility in Design of Polyethylene Terephthalate (PET) Hydrolases

The accumulation of polyethylene terephthalate (PET), a widely used polyester plastic in packaging and textiles, poses a global environmental crisis. Biodegradation presents a promising strategy for PET recycling, with PET hydrolases (PETase) undertaking the task at the molecular level. Unfortunately, due to its low thermostability, PETase can only operate at ambient temperatures with low PET depolymerization efficiency, hindering its practical application in industry. Currently, efforts to engineer PETase have primarily focused on enhancing its thermostability. However, increased stability often reduces the structural dynamics necessary for substrate binding, potentially slowing down the enzymatic activity. To elucidate the delicate balance between stability and flexibility in optimizing PETase catalytic activity, we performed theoretical investigations on both wild-type PETase (WT-PETase) and a thermophilic variant (Thermo-PETase) using molecular dynamics simulations and frustration analysis. Despite being initially designed to stabilize the native structure of enzyme, our findings reveal that Thermo-PETase exhibits an unprecedented increase in structural flexibility at the PET binding and catalytic sites, beneficial for substrate recruitment and product release, compared to WT-PETase. Upon PET binding, we observed that structural dynamics of Thermo-PETase are largely quenched, facilitating subsequent chemical reactions. Compared to WT-PETase, Thermo-PETase forms more extensive interactions with PET, resulting in a higher population of catalytically competent enzyme-substrate states, thus contributing to increased catalytic activity. Our theoretical results are consistent with experimental findings and further suggest that Thermo-PETase exhibits higher catalytic activity than WTPETase across a broad temperature range by leveraging stability and flexibility at high and low temperatures, respectively. Our findings offer valuable insights into how PETase optimizes its enzymatic performance by balancing stability and flexibility, paving the way for future PETase design strategies.

biophysics↗

bioRxiv2024

Investigation of the mechanism of accelerated biodegradation of Paracoccus-KDSPL-02

Paracoccus-KDSPL-02 can accelerate to degrade penicillin G under light remain poorly understood, largely due to the lack of high-throughput genome engineering tools. Firstly, this study sequenced the genome of Paracoccus-KDSPL-02 and mined the genes that might be involved, and in order to understand in detail whether the expression of the mined genes changed during light. Further, for genes with altering transcriptional levels under light, this study obtained PROKKA_01468 which a photoreceptor protein in Paracoccus-KDSPL-02. In the end, for validating the function of PROKKA_01468, this study knocked down the sequence of the PROKKA_01468 by applying gene editing system, and the knockdown strain showed significant change in the rate of degradation of phenylacetic acid, which is the intermediate product of penicillin G degradation, by light compared with darkness, so that the PROKKA_01468 is the most effective photoreceptor protein in Paracoccus-KDSPL-02. SynopsisThis research elucidates a molecular mechanism capable of accelerating penicillin G degradation in wastewater, with significant implications for environmental science.

bioengineering↗

bioRxiv2024

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

BackgroundEndoplasmic reticulum (ER) stress signaling pathways have pivotal roles in atherosclerosis progression. Recently, we have developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP) and consequently saves intracellular ATP consumption and mitigates ER stress. Methods and ResultsWe assessed the efficacy of KUS121 against atherosclerosis by its daily injection into Apoe-/- mice fed with Western Diet (WD) for 8 weeks. Consequently, KUS121 treatment reduced atherosclerosis progression by approximately 40% in atherosclerotic plaques. Interestingly, we found that C/EBP homologous protein (CHOP), an established ER stress marker, was mainly expressed in plaque endothelium. Therefore, we assessed the action of KUS121 in endothelial cells using the human endothelial cell line (EA.hy926 cells). As a result, KUS121 prevented ER stress-induced apoptosis and downregulated the IRE1 (Inositol-requiring enzyme) -associated inflammatory pathways. Consistent with these in vitro findings, KUS121 treatment also significantly reduced endothelial apoptosis assessed by TUNEL staining and inflammation examined by immunostaining of Nuclear factor kappa B (NF-{kappa}B) and Intercellular adhesion molecule (ICAM) 1 at plaque endothelium. We also demonstrated that KUS121 maintained ATP levels in EA.hy926 cells and atherosclerotic plaque lesions using the single-wavelength or the FRET-based fluorescent ATP sensor. Supplementation of intracellular ATP by Methyl pyruvate (MePyr) attenuated ER stress-induced apoptotic and inflammatory pathways in endothelial cells, which could be the main mechanism how KUS121 reduces ER stress. ConclusionsKUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels and attenuating ER stress-induced apoptosis and inflammation in plaque endothelium.

pathology↗

bioRxiv2024

The role of evolving niche choice in herbivore adaptation to host plants

Individuals living in heterogeneous environments often choose microenvironments that provide benefits to their fitness. Theory predicts that such "niche choice" can promote rapid adaptation to novel environments and help maintain genetic diversity. An open question of large applied importance is how niche choice and niche choice evolution affect the evolution of insecticide resistance in phytophagous insects. We, therefore, developed an individual-based model based on phytophagous insects to examine the evolution of insecticide resistance and host plant choice via oviposition preferences. To find biologically realistic parameter ranges, we performed an empirical literature survey on insecticide resistance in major agricultural pests and also conducted a density-dependent survival experiment using potato beetles. We find that, in comparison to a scenario where individuals randomly oviposit eggs on toxic or non-toxic plants, the evolution of niche choice generally leads to slower evolution of resistance and facilitates the coexistence of different phenotypes. Our simulations also reveal that recombination rate and dominance effects can influence the evolution of both niche choice and resistance. Thus, this study provides new insights into the effects of niche choice on resistance evolution and highlights the need for more studies on the genetic basis of resistance and choice.

evolutionary biology↗

bioRxiv2024

ZNF574 is a Quality Control Factor For Defective Ribosome Biogenesis Intermediates

Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that take part in numerous interdependent steps. This complexity creates a large genetic space in which pathogenic mutations can occur. "Dead-end" ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control pathway(s) that monitor ribosome assembly. However, the factors that differentiate between on-path and dead-end intermediates are unknown. We engineered a system to perturb ribosome assembly in human cells and discovered that faulty ribosomes are degraded via the ubiquitin proteasome system. We identified ZNF574 as a key component of a novel quality control pathway, which we term the Ribosome Assembly Surveillance Pathway (RASP). Loss of ZNF574 results in the accumulation of faulty biogenesis intermediates that interfere with global ribosome production, further emphasizing the role of RASP in protein homeostasis and cellular health.

cell biology↗

bioRxiv2024

Linkage: an interactive shiny app and R package for linking of DNA regulatory peaks to genes

SummaryExisting studies have demonstrated that the integration analysis of transcriptomic and epigenomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, such investigations on large-scale sequencing data remain challenging for researchers or clinicians with limited bioinformatics knowledge. To facilitate the interpretation of gene regulatory landscape, we developed an R Shiny application and R package [Linking of atac-seq to gene expression data (Linkage)] for exploring and visualizing potential cis-regulatory elements (CREs) of genes based on ATAC-seq and RNA-seq data. Linkage offers six modules to systematically identify, annotate, and interpret potential gene regulatory elements from the whole genome step by step. Linkage can provide interactive visualization for the correlation between chromatin accessibility and gene expression. More than that, Linkage identifies transcription factors (TFs) that potentially drive the chromatin changes through identifying TF binding motifs within the CREs and constructing trans-regulatory networks of the target gene set. This powerful tool enables researchers to conduct extensive multiomics integration analysis and generate visually appealing visualizations that effectively highlight the relationship between genes and corresponding regulatory elements. With Linkage, users can obtain publishable results and gain deeper insights into the gene regulatory landscape. Availability and implementation Linkage is freely available as a Shiny web application (https://xulabgdpu.org.cn/linkage) and an R package (https://github.com/XuLab-GDPU/Linkage). The documentation is available at (https://aicplane.github.io/Linkage-tutorial/).

bioinformatics↗

bioRxiv2024

Herbivory can increase plant fitness via reduced interspecific competition. Evidence from models and mesocosms

Herbivores are generally considered to reduce plant fitness. However, as in natural communities herbivores often feed on several competing plant species, herbivores can also increase plant fitness by reducing interspecific competition among plants. In this study, we developed a testable model to predict plant fitness in the presence of an interspecific competitor and an herbivore that feeds on both plant species. Our model allows to predict at which herbivore and competitor densities the focal species will benefit from herbivory. This can be estimated by quantifying the effects of the herbivore on the fitness of the focal plant and on its competitor, and by estimating the levels of intra- and interspecific competition in a pair-wise fashion, respectively. We subsequently validated the model in indoor microcosms using three interacting species: an aquatic macrophyte (the giant duckweed Spirodela polyrhiza), its native competitors (green algae), and its native herbivore (the pond snail Lymnaea stagnalis). Additional outdoor mesocosm experiments supported our model under natural conditions. Together, this study provides a conceptual framework to understand how herbivores shape plant fitness in a community context.

ecology↗